This resubmission of my INDEPENDENT SCIENTIST AWARD (K-02) will maintain me as a research scientist and mentor in the substance abuse treatment research I began under my K-20. As a psychopharmacologist, child psychiatrist, and addiction psychiatrist, I have been investigating early intervention to prevent career addiction. As a former high school teacher, I established, during my K-20, a referral network from which to recruit high-risk subjects. The Career Development and Research Plans hypothesize pathological affective (i.e. non predatory) aggression is a major psychopharmacologically relevant problem in antisocial spectrum disorders, including substance abuse. The Research Plan operationalizes criteria for a hypothetical subtype of affective aggression characterized by irritable mood swings. The Research Plan tests divalproex (i.e. mood stabilizer) efficacy in this subtype via three six-week randomized clinical trials, first in adolescents, then in children and finally in adults. Research Plan revisions incorporate IRG suggestions to use the referral network to supplement tracking of medication compliance and to follow-up children long after they have returned to the community. The Career Development Plan is more detailed in this resubmission. Part One will develop screening criteria for other affective (i.e. non-predatory) aggressive storms (e.g. impulsive, paranoid, depressive) and refine them using response to specific pharmacological agents (e.g stimulants, low dose antipsychotics, SSRI's, respectively). Part Two proposes to impute medication effectiveness if efficacious medication alters intermediate steps in the antisocial trajectory. These "surrogate outcomes" include educational tracking into aggressive classes, predominance of coercive family interaction, and (for irritable affective aggression), marijuana use. If efficacious medication alters these surrogates, it is probably making a difference. If not, we must rethink our causal, models. Developing these ideas requires protected time to study epidemiology/biostatistics and work with my collaborators. A course of study at the School of Public Health was developed after consultation with Drs. Ezra Susser and Peter Jensen. Dr. Pardes' letter clarifies that Columbia's ability to support this Career Development Plan is contingent on continued financial support from NIDA-K. Concrete plans for participation in research ethics seminars are provided. Mentoring is via 2 NIH Training Fellowships at Columbia: Dr. Kleber's Substance Abuse Training Fellowship and the Psychiatric Epidemiology Training Program. I mentor child psychiatrists seeking advanced training in addiction and teacher to pre and post doctoral students interested in substance abuse intervention and randomized clinical trials.